The goal of this K99/R00 Career Development Plan is to launch an independent research program in reproductive and environmental epidemiology of endocrine-disrupting chemicals (EDCs) which includes evaluating social determinants of health that may affect overlapping biologic pathways. To accomplish this goal, the candidate will enhance her expertise in environmental health sciences with didactic and hands-on training in reproductive biology, social epidemiology/stress science, and environmental epidemiologic methods. This specialized training will allow her to achieve her long term goal of becoming an independent academic investigator and offering new insights on the cumulative impacts of environmental and social factors on reproductive health. The primary goal of the candidate's Research Plan is to evaluate the independent effects of polybrominated diphenyl ethers (PBDEs) and psychosocial stress on thyroid hormone disruption and consequent perinatal outcomes among a population of socioeconomically and racially diverse pregnant women. This work is particularly innovative as both PBDEs and psychosocial stress can impact the thyroid system, suggesting a biologic plausibility for interaction;however the two exposures have never been examined simultaneously in a human study. During the K99 mentored phase, under the primary mentorship of Dr. Tracey Woodruff, the candidate will use innovative measures to characterize biologically-relevant exposures to PBDEs and psychosocial stress and their effects on thyroid hormone disruption. Exposure to PBDEs will be assessed using both PBDE congeners as well as their hydroxylated metabolites (OH-PBDEs). Psychosocial stress will be evaluated with subjective measures of stress and telomere length, a biomarker of cellular aging that is influenced by psychosocial stress. In the independent phase, the candidate will apply this knowledge to investigate the independent effects of PBDEs and psychosocial stress on adverse perinatal outcomes, such as gestational hypertension, preterm birth, and low birth weight, and assess whether these effects are mediated via the thyroid system. The integration of this work will enable the candidate to develop the necessary methodological and biological frameworks to examine the combined, and potentially synergistic, effects of environmental and psychosocial factors on perinatal outcomes in future R01 studies. The candidate is well positioned to accomplish these goals at the University of California, San Francisco, a highly respected research institution, with a strong environmental reproductive health program, a world-renowned faculty with expertise in psychosocial stress, and an extensive biomedical infrastructure. The primary mentor and co-mentors in reproductive sciences, environmental epidemiology, health disparities, stress science, and biostatistics will guide the process whereby the candidate learn the methods that are required to accomplish the goals set forth in this proposal. This project represents the cutting-edge of health disparities and environmental health research and seeks to answer critical scientific as well as policy-relevant questions for improving the health of vulnerable populations who often face disproportionate and elevated exposures to multiple chemical and non-chemical stressors. Public Health Relevance: The goal of this project is to prepare Dr. Ami Zota to transition to a position as an independent academic investigator in environmental health sciences focusing on the consequence of endocrine-disrupting chemicals (EDCs) during pregnancy and social factors that may affect overlapping biologic pathways. She will conduct epidemiologic analyses to investigate the effects of polybrominated diphenyl ether (PBDE) flame retardants and psychosocial stress on perinatal outcomes and assess whether these effects are mediated by the thyroid system. Results from this work will improve pregnancy outcomes and inform public health policy, particularly for vulnerable subpopulations, who often encounter elevated exposures to chemical and non-chemical stressors.